Nucleic acid-based molecules, such as DNA, RNA, and PNA, have continued to find ever-increasing levels of implementation and exciting applications in biology and biomedical systems, whether for gene knockout, as aptamers, for drug delivery and targeting, in biodetection, and in many other areas.
DNA is one of the most capable and powerful molecules: functional as genetic material or as aptamers, hybridizing to complementary strands, active in transcription/translation and able to induce organization and formation of nanostructures. Unfortunately, technical utilization of DNA remains prohibitively expensive and/or difficult to implement in any but the most valuable applications, particularly as materials. As a synthetic alternative, peptide nucleic acids (PNAs) were developed and found to hybridize with complimentary PNA or DNA molecules.
The first PNA was synthesized using an aminoethylglycine (AEG) backbone, which was selected based on rudimentary molecular modeling that indicated similar repeat-unit distances and optimized bond angles to that of the phosphate-ribose backbone of DNA. Since its discovery, several variations of PNAs have been synthesized and evaluated, revealing basic structural constraints required for hybridization. The most critical constraint appears to be the distance between pendant nucleobases along the backbone of the chain—the optimum of which is six atoms. While hybridization with ssDNA has been observed for PNAs possessing a 5- or 7-atom spacer between nucleobases, PNA backbone variations having a 6-atom spacer exhibit greater stability as indicated by their higher melting temperatures. PNAs have been used extensively in self-assembly and targeted drug delivery. Despite PNA's advantages over DNA, they are limited by the characteristics of the formation reactions as well as the peptidic backbone. Among those problems are the need for large reactant excesses, relatively slow reaction kinetics, and numerous concerns over side reactions. Thus, there is a need for additional nucleic acid mimetics. The current disclosure meets this need.